Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.

Spontaneous Pneumothorax Due to Ruptured Bulla of the Azygos Lobe.

Azygos lobe is an uncommon anatomic variant that is widely recognized, but rarely associated with pneumothorax. We present a successful surgical management of a spontaneous pneumothorax resulting from rupture of a bulla in an incidentally discovered azygos lobe. The patient is a 73-year-old man who presented with the first-time occurrence of a spontaneous right pneumothorax.

Computationally Optimized Hemagglutinin Proteins Adjuvanted with Infectimune Generate Broadly Protective Antibody Responses in Mice and Ferrets.

Standard-of-care influenza vaccines contain antigens that are typically derived from components of wild type (WT) influenza viruses. Often, these antigens elicit strain-specific immune responses and are susceptible to mismatch in seasons where antigenic drift is prevalent. Thanks to advances in viral surveillance and sequencing, influenza vaccine antigens can now be optimized using computationally derived methodologies and algorithms to enhance their immunogenicity.

The relationship between discordant birth weight in twin pairs and the development of retinopathy of prematurity.

The association of low birth weight and development of retinopathy of prematurity (ROP) is well established for singletons; however, the association of birth weight and ROP in twins of discordant weight is understudied. Using an ROP registry, we investigated whether smaller twins were at greater risk for developing any stage ROP (stage 1 or greater in either eye) compared with their larger siblings, after adjusting for birth weight and gestational age. Discordance was defined as a birth weight difference of >25%.

Flumazenil may improve gait and mentation in dogs presenting with marijuana toxicosis.

Introduction: Alongside the United States' growing landscape of legalized recreational marijuana intended for humans, cases of canine marijuana toxicosis have been on the rise. Most commonly these dogs have mild clinical signs and respond well to supportive therapies. However, patients might still be ataxic, unable to walk, or remain heavily sedated at the time of discharge.

The potential of AB-free kava in enabling tobacco cessation via management of abstinence-related stress and insomnia: study protocol for a randomized clinical trial.

Background: As the primary cause of various preventable illnesses, smoking results in approximately five million premature deaths each year in the US and a multitude of adults living with serious illness. The majority of smokers know the health risks associated with smoking and intend to quit. However, quitting is very difficult partly because of insomnia and stress associated with it.

Self-organization of the hematopoietic vascular niche and emergent innate immunity on a chip.

Here, we present a bioengineering approach to emulate the human bone marrow in vitro. Our developmentally inspired method uses self-organization of human hematopoietic stem and progenitor cells and vascular endothelial cells cultured in a three-dimensional microphysiological system to create vascularized, perfusable tissue constructs that resemble the hematopoietic vascular niche of the human marrow. The microengineered niche is capable of multilineage hematopoiesis and can generate functionally mature human myeloid cells that can intravasate into perfused blood vessels, providing a means to model the mobilization of innate immune cells from the marrow.

Flavokavains A- and B-Free Kava Enhances Resilience against the Adverse Health Effects of Tobacco Smoke in Mice.

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onset of numerous preventive diseases and imposing significant health burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco-smoking-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use.

Resolution of Historically Discordant Ames Test Negative / Rodent Carcinogenicity Positive N-nitrosamines using a Sensitive, OECD-aligned Design.

The in vitro Bacterial Reverse Mutation (Ames) Test is crucial for evaluating the mutagenicity of pharmaceutical impurities. For N-nitrosamines (NAs) historical data indicated that for certain members of this chemical class the outcomes of the Ames Test did not correlate with their associated rodent carcinogenicity outcomes. This has resulted in negative outcomes in an OECD aligned Ames Test alone (standard or enhanced) no longer being considered sufficient by regulatory authorities to assess potential carcinogenic risk of NAs if present as impurities in drug products.

Industrial Genotoxicology Group (IGG): 36th Annual Meeting Report.

The proceedings of the 36th annual meeting of the Industrial Genotoxicology Group (IGG) are shared here. The meeting held at Lhasa Limited, Leeds, UK on 28th November 2023, focussed two aspects; New Approach Methodologies (NAM's), including those for the assessment of non-standard modalities such as gas-vapour assessments and nanomaterials, and addressing the regulatory challenges associated with understanding the genotoxic and carcinogenic potential of N-nitrosamines and N-nitrosamine impurities. New approach methodologies, such as error-corrected sequencing and enhanced Ames tests that may help address these challenges were also discussed.

Comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban in dogs.

Background: Comparative pharmacokinetics and pharmacodynamics (PK/PD) of apixaban and rivaroxaban have not been studied in dogs and the propensity of these drugs to cause hypercoagulability after discontinuation is unknown.

Hypothesis: Compare the PK/PD of clinical dosing regimens of PO apixaban and rivaroxaban administered repeatedly to healthy dogs and assess the effect of abrupt drug discontinuation on coagulation.

Animals: Six University-owned, purpose-bred, middle-aged, mixed-breed dogs (4 male, 2 female).

Bioethics at the bedside: considering the adolescent voice in withdrawal of life-sustaining therapy.

Durable mechanical circulatory devices are commonly used to support children and adolescents in end-stage heart failure. However, these patients remain at high risk of acute medical complications, which may lead to significant impairment in functional capacity, altered quality of life, or death. We explore the incorporation of adolescent directives into medical decision-making in this scenario through a clinical case vignette.

Ketamine Terminating Persistent Ventricular Tachycardia.

Ventricular tachycardia (VT) is an arrhythmia associated with sudden cardiac death. VT storm is a complication of persistent VT requiring immediate antiarrhythmic therapy. In refractory cases, adjunctive therapy includes sedation/mechanical ventilation or catheter ablation.

Association Between Systemic Levels of Vascular Endothelial Growth Factor and Optical Coherence Tomography Biomarkers in a Non-Neovascular Age-Related Macular Degeneration Cohort.

Background And Objective: Investigate associations between systemic vascular endothelial growth factor (VEGF) and optical coherence tomography (OCT) biomarkers in eyes with complete retinal pigment epithelium and outer retina atrophy (cRORA) secondary to non-neovascular age-related macular degeneration.

Patients And Methods: Cross-sectional study of patients with cRORA. OCT images and blood samples were collected at study enrollment.

Artificial Intelligence- and Physician-Interpreted Stool Image Characteristics Correlate With C-Reactive Protein Among Inpatients With Acute Severe Ulcerative Colitis: A Pilot Study.

Background: Stool characteristics are used as a measure of ulcerative colitis (UC) disease activity, but they have not been validated against objective inflammation. We aimed to determine whether stool characteristics measured by trained artificial intelligence (AI) and physicians correlate with inflammation in UC.

Methods: Patients hospitalized with acute severe UC (ASUC) were asked to capture images of all bowel movements using a smartphone application (Dieta®).